The acquired immunodeficiency syndrome (AIDS) is a global pandemic with over 18 million human immunodeficiency virus (HIV)-infected individuals worldwide. A major focus within our laboratory has been on defining the unique epidemiologic, clinical, virologic and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In Pune, India, we established a prospective cohort of over 3,000 high-risk individuals attending STD clinics, of whom 23% were seropositive for HIV- 1. In a cohort of HIV-1 seronegative individuals followed over 15 months, the HIV incidence was 12.2% per year with rates as high as 28.6% for commercial sex workers. Recurrent genital ulcers and non-ulcerative STDs were independently associated with an 11 and 19-fold increased risk of HIV seroconversion, respectively. Phylogenetic analysis of viral strains isolated from these individuals demonstrate dissemination of both clade B and C strains with high-titer neutralizing antibody against clade B isolates. Additional studies among patients presenting to the Johns Hopkins Emergency Department demonstrated a rise in seroprevalence to 12.5% among 2,000 patients. A seroprevalence of 6.6% was documented by rapid HIV testing performed in the Emergency Department among patients of unknown serostatus. In a multi-center study comparing foscarnet and ganciclovir for the treatment of CMV retinitis, we demonstrated a significant decline in HIV-1 viral load in both treatment arms primarily due to their anti-viral effect on CMV replication. In perinatal studies in Zaire, Haiti, Malawi, and the U.S., we documented a 28% perinatal transmission rate. Utilizing HIV culture and PCR we estimated that 31% were infected in utero, 58% intrapartum, and 11% postnatally. In studies of HIV-1 and HTLV-1 co-infection in Brazil, we documented a higher incidence of myelopathy and peripheral neuropathy among dually infected individuals. In addition, T and B cell responses to pneumococcal and tetanus immunizations were markedly diminished among dually infected individuals compared to those infected with HIV-1 alone. Further studies are planned to further elucidate the immunologic modulations of HIV infection by co-infection with HTLV in these cohorts.